U.S. Pat. No. 4,174,453 granted Nov. 13, 1979, which is hereby incorporated by reference, filed May 22, 1978, which is a continuation-in-part of U.S. Pat. application Ser. No. 698,589, filed June 22, 1976, itself a divisional of U.S. Pat. application Ser. No. 522,145, granted Nov. 9, 1976 as U.S. Pat. No. 3,991,199, which is hereby also incorporated by reference, filed Nov. 8, 1974 (and which is a continuation-in-part of U.S. Pat. application No. 422,613, filed Dec. 16, 1973 and now abandoned) by Joel G. Berger, the inventor herein, disclosed a process for the stereoselective reduction of certain indoles of the formula: ##STR1## wherein X is hydrogen or certain halogen, alkyl or alkoxy groups,
Y is hydrogen or trifluoromethyl, and PA1 R is hydrogen or certain organic radicals PA1 R.sub.2 can be an alkyl of 1 through 5 carbon atoms, benzyl, benzyl substituted with methyl, methoxy or chloro; phenethyl, 3-phenylpropyl, 3-phenylpropyl with the phenyl ring substituted with chloro, bromo, or methoxy; C.sub.3 -C.sub.5 -cycloalkyl; furfuryl; 2-thenyl; C.sub.4 -C.sub.8 cycloalkyl=methyl; (methylcyclopropyl)methyl; (cis-2,3-dimethyl=cyclopropyl)methyl; exo-7-norcarylmethyl; (4-methyl=bicyclo[2.2.2]oct-1-yl)methyl; (bicyclo[2.2.1]hept-2=yl)methyl; 1-adamantylmethyl, or a 2-adamantylmethyl group; PA1 R.sub.3 can be hydrogen or alkyl of 1 through 4 carbon atoms; PA1 R.sub.4 can be (a) phenyl, (b) phenyl substituted with one or more halogen, NH.sub.2, NHR, N(R).sub.2, OR, SR or CF.sub.3 groups, (c) a carbon chain, (d) a carbon chain substituted with one or more halogen, OR, SR, NH.sub.2, NHR, N(R).sub.2 or CF.sub.3 groups, or (e) a carbon chain interrupted by oxygen, sulfur, or nitrogen, or can be linked with R.sub.1 to form an ethylene group; PA1 R.sub.5 can be (a) hydrogen, (b) phenyl, (c) phenyl substituted with one or more halogen, NH.sub.2, NHR, N(R).sub.2, OR, SR, or CF.sub.3 groups, (d) a carbon chain, (e) a carbon chain substituted with one or more halogen, OR, SR, NH.sub.2, NHR, N(R).sub.2 or CF.sub.3 groups, or (f) a carbon chain interrupted by oxygen, sulfur, or nitrogen; or can be linked with R.sub.6 to form an o-phenyleneethylene group; PA1 R.sub.6 can be linked with R.sub.5 to form an o-ethylenephenylene group; or PA1 R.sub.6 -R.sub.9 can each be independently selected from (a) hydrogen, halogen, OR, SR, NH.sub.2, NHR, N(R).sub.2 or CF.sub.3, (b) a carbon chain interrupted by oxygen, sulfur, or nitrogen; PA1 R.sub.10 can be hydrogen, methyl or ethyl; in which R can be an alkyl group of 1 through 5 carbon atoms. PA1 R.sub.1 and R.sub.4 are joined and taken together are an ethylene group; PA1 R.sub.2 is benzyl; benzyl ring-substituted with methyl, methoxy, or chloro; phenethyl: 3-phenylpropyl; 3-phenylpropyl ring substituted with chloro, bromo, or methoxy; furfuryl; 2-thenyl; C.sub.1 -C.sub.5 alkyl; C.sub.3 -C.sub.7 cycloalkyl; C.sub.4 -C.sub.8 cycloalkylmethyl; (methyl=cyclopropyl)methyl; (cis-2,3-dimethylcyclopropyl)=methyl; exo-7-norcarylmethyl; (4-methylbicyclo[2.2.2]=oct-1-yl)methyl; (bicyclo[2.2.1]hept-2-yl)methyl; 1-adamantylmethyl; or 2-adamantylmethyl; PA1 R.sub.3 is hydrogen; ##STR7## R.sub.6 is hydrogen; R.sub.7 is hydrogen; PA1 R.sub.8 is X; and PA1 R.sub.9 is hydrogen; PA1 (1) trans-2,3,4,4a,5,8b-hexahydro-5-phenyl-1H-=pyrido[4,3-b]indole, because its analgesic activity is separated from its sedative activity by a 10-fold difference in dose. PA1 (2) and (3) trans-2-(1-adamantylmethyl)-2,3,4,4a,5,9b-=hexahydro-5-phenyl-1H-pyrido[4, 3-b]indole and trans-2-(2-adamantylmethyl)-2,3,4,4a,5,9b-=hexahydro-5-phenyl-1H-pyrido[4, 3-b]indole, because they exhibit minor tranquilizing (anxiolytic) activity at doses which are not sedating. They also exhibit major tranquilizing (antipsychotic) activity. PA1 (4) trans-2,3,4,4a,5,9b-hexahydro-2-(exo-7-norcaryl=methyl)-5-phenyl-1H-pyrido [4,3-b]indole, because of its potency in reducing locomotor activity. PA1 (5), (6), (7), and (8) trans-2-ethyl-, trans-2-=cyclobutylmethyl)- and trans-2-(cyclopentyl=methyl)-2,3,4,4a,5,9b-hexahydro-5-phenyl-1H-=pyrido[4 ,3-b]indole, and trans-8-bromo-5-=(4-bromophenyl)-2,3,4,4a,5,9b-hexahydro-2-=methyl-1H-pyri do[4,3-b]indole because of their major tranquilizer (antipsychotic) activity. PA1 R.sub.2 is hydrogen, alkyl of 1 through 3 carbon atoms, PA1 R.sub.3 is hydrogen, methyl or ethyl; PA1 R.sub.5 is phenyl; PA1 R.sub.6, R.sub.7, R.sub.8 and R.sub.9 are hydrogen; and PA1 R.sub.10 is hydrogen, methyl or ethyl; provided that the total number of carbon atoms in R.sub.2 +R.sub.3 +R.sub.10 is not less than one and not more than four, and provided further that one of R.sub.3 or R.sub.10 must be other than hydrogen. PA1 R.sub.2 is ethyl; PA1 R.sub.3 is methyl; PA1 R.sub.5 is phenyl; and PA1 R.sub.6, R.sub.7, R.sub.8, R.sub.9 and R.sub.10 are hydrogen. PA1 R.sub.1 and R.sub.4 are joined and taken together to form an ethylene group; PA1 R.sub.2 is benzyl; benzyl ring-substituted with methyl, methoxy, or chloro; phenethyl; 3-phenylpropyl-=3-phenylpropyl ring substituted with chloro, bromo, or methoxy; furfuryl; 2-thenyl; C.sub.1 -C.sub.5 alkyl; cyclopropyl; C.sub.4 -C.sub.8 cycloalkylmethyl; (methylcyclopropyl)methyl; exo-7-norcarylmethyl; (4-methybicyclo[2.2.2]oct-1-yl)methyl; (bicyclo=[2.2.1]hept-2-yl)methyl; 1-adamantylmethyl or 2-adamantylmethyl; PA1 R.sub.3 is hydrogen; PA1 R.sub.5 and R.sub.6 are joined and taken together to form ##STR8## R.sub.7, R.sub.8, and R.sub.9 are all hydrogen. PA1 (1) reaction of the indole-containing molecule in the form of the strong acid salt, which results in PA1 (2) acidification of the reaction product of step (1)
said process comprising reacting the compounds of formula I with borane/tetrahydrofuran, followed by treatment with acid.
Similarly, U.S. Pat. No. 3,932,650, granted Jan. 13, 1976 to Charles D. Adams, which is hereby incorporated by reference, discloses a process for the stereoselective reduction of certain other indoles of the formula: ##STR2## where R is certain organic radicals, said process being substantially as mentioned immediately above and in U.S. Pat. No. 3,991,199.
U.S. Pat. No. 4,091,102 which is hereby incorporated by reference, filed June 22, 1976 (and which is a continuation-in-part of U.S. Pat. application Ser. No. 606,871, filed Aug. 22, 1975, and now abandoned), granted May 23, 1978, to Sonia Ruth Teller, discloses a process for the stereoselective reduction of certain indoles of the formula: ##STR3## where R.sub.1, R.sub.2 and R.sub.3 are hydrogen or certain organic radicals, the process being substantially as mentioned immediately above, and in U.S. Pat. No. 3,991,199.
The novel compounds disclosed in the above-identified patents and patent applications, which compounds heretofore have been produced by the reduction consisting of reaction with BH.sub.3 /THF followed by treatment with acid disclosed there, are useful as pharmaceutical materials and/or as intermediates for the synthesis of other pharmaceutical materials.
For example, the novel compounds disclosed in U.S. Pat. No. 3,890,327, which is hereby incorporated by reference, granted June 17, 1975 to Joel G. Berger, and the novel compounds disclosed in U.S. Pat. No. 4,018,930, which is hereby incorporated by reference, granted Apr. 19, 1977 (and which is a continuation-in-part of U.S. Pat. application Ser. No. 422,615, filed Dec. 6, 1973, now abandoned) by Joel G. Berger: ##STR4##
where R is hydrogen, certain organic radicals or COOR.sub.1 can all be made, directly or indirectly, from certain of the compounds disclosed in U.S. Pat. No. 3,932,650, mentioned above.
The use of BH.sub.3 /THF suffers from several disadvantages, most notably the requirement that the primary reagent be used in large excess and the fact that this reagent is toxic, flammable and generally difficult and inconvenient to use. In addition, destruction of the excess reagent is hazardous.